RT Journal Article
SR Electronic
T1 Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101299
DO 10.26508/lsa.202101299
VO 5
IS 10
A1 Chiao-Yu Hsieh
A1 Ching-Chih Tu
A1 Jui-Hung Hung
YR 2022
UL https://www.life-science-alliance.org/content/5/10/e202101299.abstract
AB The connectivity among signatures upon perturbations curated in the CMap library provides a valuable resource for understanding therapeutic pathways and biological processes associated with the drugs and diseases. However, because of the nature of bulk-level expression profiling by the L1000 assay, intraclonal heterogeneity and subpopulation compositional change that could contribute to the responses to perturbations are largely neglected, hampering the interpretability and reproducibility of the connections. In this work, we proposed a computational framework, Premnas, to estimate the abundance of undetermined subpopulations from L1000 profiles in CMap directly according to an ad hoc subpopulation representation learned from a well-normalized batch of single-cell RNA-seq datasets by the archetypal analysis. By recovering the information of subpopulation changes upon perturbation, the potentials of drug-resistant/susceptible subpopulations with CMap L1000 were further explored and examined. The proposed framework enables a new perspective to understand the connectivity among cellular signatures and expands the scope of the CMAP and other similar perturbation datasets limited by the bulk profiling technology.